Emapalumab treatment in rheumatologic disease-associated hemophagocytic lymphohistiocytosis: a plain language summary

Shanmuganathan Chandrakasan¹, Carl E Allen², Deepika Bhatla³, John Carter⁴, May Chien⁵, Robert Cooper⁶, Lauren Draper³, Olive S Eckstein², Rabi Hanna⁷, J Allyson Hays⁸, Michelle L Hermiston⁹, Ashley P Hinson¹⁰, Patricia M Hobday¹¹, Michael S Isakoff¹², Michael B Jordan^{13

14

15}, Jennifer W Leiding^{16

17}, Renee Modica¹⁸, Taizo A Nakano¹⁹, Abiola Oladapo²⁰, Sachit A Patel²¹, Priti Pednekar²², Mona Riskalla¹¹, Susmita N Sarangi²³, Prakash Satwani²⁴, Anand Tandra²⁵, Kelly J Walkovich²⁶, John D Yee²⁰, Adi Zoref-Lorenz^{15

27}, Edward M Behrens²⁸; REAL-HLH Investigators

Affiliations

¹ aDivision of Bone and Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
² bDivision of Pediatric Hematology and Oncology, Baylor College of Medicine, Houston, Texas, USA.
³ cSaint Louis University, St Louis, Missouri, USA.
⁴ dOregon Health and Science University, Portland, Oregon, USA.
⁵ eLucile Packard Children's Hospital at Stanford University, Palo Alto, California, USA.
⁶ fBellflower Medical Center, Bellflower, California, USA.
⁷ gCleveland Clinic Children's Hospital, Cleveland, Ohio, USA.
⁸ hChildren's Mercy Hospital, Kansas City, Missouri, USA.
⁹ iUniversity of California, San Francisco, San Francisco, California, USA.
¹⁰ jAtrium Health, Levine Children's Hospital, Charlotte, North Carolina, USA.
¹¹ kDivision of Rheumatology, Allergy and Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
¹² lConnecticut Children's Medical Center, Hartford, Connecticut, USA.
¹³ mDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁴ nDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹⁵ oDivision of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁶ pDivision of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁷ qInstitute for Clinical and Translational Research and the Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Florida, USA.
¹⁸ rUniversity of Florida Health, Gainesville Shands Children's Hospital, Gainesville, Florida, USA.
¹⁹ sChildren's Hospital, Aurora, Colorado, USA.
²⁰ tSobi, Inc., Waltham, Massachusetts, USA.
²¹ uUniversity of Nebraska Medical Center, Omaha, Nebraska, USA.
²² vPRECISIONheor, Bethesda, Maryland, USA.
²³ wGeorgetown University Hospital-Medstar, Washington, District of Columbia, USA.
²⁴ xColumbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York, USA.
²⁵ yFranciscan Health, Indianapolis, Indiana, USA.
²⁶ zDivision of Pediatric Hematology Oncology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
²⁷ †Hematology Institute, Meir Medical Center, School of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁸ ‡Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

PMID: 40528399
PMCID: PMC12506739
DOI: 10.1080/1750743X.2025.2509478

Emapalumab treatment in rheumatologic disease-associated hemophagocytic lymphohistiocytosis: a plain language summary

Shanmuganathan Chandrakasan et al. Immunotherapy. 2025 May.

. 2025 May;17(7):461-478.

doi: 10.1080/1750743X.2025.2509478. Epub 2025 Jun 17.

Authors

Affiliations

¹ aDivision of Bone and Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia, USA.
² bDivision of Pediatric Hematology and Oncology, Baylor College of Medicine, Houston, Texas, USA.
³ cSaint Louis University, St Louis, Missouri, USA.
⁴ dOregon Health and Science University, Portland, Oregon, USA.
⁵ eLucile Packard Children's Hospital at Stanford University, Palo Alto, California, USA.
⁶ fBellflower Medical Center, Bellflower, California, USA.
⁷ gCleveland Clinic Children's Hospital, Cleveland, Ohio, USA.
⁸ hChildren's Mercy Hospital, Kansas City, Missouri, USA.
⁹ iUniversity of California, San Francisco, San Francisco, California, USA.
¹⁰ jAtrium Health, Levine Children's Hospital, Charlotte, North Carolina, USA.
¹¹ kDivision of Rheumatology, Allergy and Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
¹² lConnecticut Children's Medical Center, Hartford, Connecticut, USA.
¹³ mDivision of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁴ nDepartment of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
¹⁵ oDivision of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
¹⁶ pDivision of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁷ qInstitute for Clinical and Translational Research and the Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Florida, USA.
¹⁸ rUniversity of Florida Health, Gainesville Shands Children's Hospital, Gainesville, Florida, USA.
¹⁹ sChildren's Hospital, Aurora, Colorado, USA.
²⁰ tSobi, Inc., Waltham, Massachusetts, USA.
²¹ uUniversity of Nebraska Medical Center, Omaha, Nebraska, USA.
²² vPRECISIONheor, Bethesda, Maryland, USA.
²³ wGeorgetown University Hospital-Medstar, Washington, District of Columbia, USA.
²⁴ xColumbia University Medical Center, NewYork-Presbyterian Hospital, New York, New York, USA.
²⁵ yFranciscan Health, Indianapolis, Indiana, USA.
²⁶ zDivision of Pediatric Hematology Oncology, Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
²⁷ †Hematology Institute, Meir Medical Center, School of Medicine, Tel Aviv University, Tel Aviv, Israel.
²⁸ ‡Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

PMID: 40528399
PMCID: PMC12506739
DOI: 10.1080/1750743X.2025.2509478

No abstract available

Plain language summary

What is this summary about?Hemophagocytic lymphohistiocytosis (HLH) is a rare disease caused by overactivation of the body’s natural defense mechanism (the immune system) against infection. In untreated HLH, uncontrolled inflammation (hyperinflammation) can cause significant damage to the body’s organs and death. HLH can occur due to genetic defects (primary HLH) or as a complication or worsening of an underlying disease such as rheumatologic disease, cancer, or infection (secondary HLH).Interferon-gamma (IFNγ) is a type of protein that is overproduced in HLH and causes hyperinflammation. Emapalumab is a medicine that blocks IFNγ activity. The REAL-HLH study described the use of emapalumab in routine clinical practice and evaluated its effects on the health of patients with HLH in the United States. This summary presents results from the REAL-HLH study for a subgroup of patients with rheumatologic disease-associated HLH, which is a particular type of secondary HLH.What were the results?Data from medical charts of patients treated for rheumatologic disease-associated HLH who received at least one dose of emapalumab were analyzed.The results from this study showed that emapalumab was used to treat patients with rheumatologic disease-associated HLH in whom HLH either worsened, recurred, or did not respond to conventional HLH treatment after initial improvement. Importantly, most patients receiving emapalumab-containing treatment regimens achieved normal or maintained stable laboratory values for ferritin, blood cell counts, liver enzymes etc., which are important HLH markers (naturally occurring molecules that serve as a sign of a normal or abnormal condition or process). In addition, physicians were able to lower the daily dose of steroids, a standard HLH medicine with long-term side effects, in most patients treated with emapalumab-containing treatment regimens (a treatment regimen is a structured and personalized plan that generally includes medications, therapies, lifestyle changes, and other interventions for managing and treating a specific medical condition or disease). Most patients (87%) were alive at the end of the study.What were the main conclusions of the REAL-HLH study reported by the researchers?Emapalumab-containing treatment regimens controlled hyperinflammation, reduced the average daily steroid dose in most patients, and were associated with a high chance of survival.[Box: see text].

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Conflict of interest statement

Dr Shanmuganathan Chandrakasan serves on the advisory boards of Sobi, Inc., Pharming Group, and Electra Therapeutics. Dr Carl Allen serves on the advisory boards of Sobi, Inc., Opna Bio, and Electra Therapeutics and has received research support from Genentech, and Opna Bio. Dr Rabi Hanna serves on the advisory boards of Vertex Pharmaceuticals, Sanofi, AbbVie, and Sumitomo Pharma Co., Ltd. and is on the speaker bureau of Sobi, Inc. and Jazz Pharmaceuticals. Dr Michelle Hermiston serves on the advisory board of Sobi, Inc. Dr Michael Jordan serves on the advisory board of Sobi, Inc. and receives research support from Sobi, Inc. and Bristol Myers Squibb. Dr Jennifer Leiding serves on the speaker/advisory boards of Sobi, Inc., Grifols, and Horizon, owns stock in bluebird bio, and is a consultant for Rocket Pharma and Prime Medicine. Dr Taizo Nakano is a consultant for Sobi, Inc. and Novartis. Dr Abiola Oladapo is an employee of Sobi, Inc. and owns stock in Sobi, Inc. Dr Sachit Patel and Dr Prakash Satwani serve on the speaker/advisory boards of Sobi, Inc. Dr Priti Pednekar was an employee of PRECISIONheor and served as a consultant of Sobi, Inc. at the time of the study. Dr Kelly Walkovich serves on the advisory boards of Sobi, Inc., Agios, and Pharming, receives research support from Pharming, serves on the advisory board and local PI for X4 Pharma. Dr John Yee was an employee of Sobi, Inc. at the time of the study. Dr Adi Zoref-Lorenz serves on the advisory board and is a consultant for Sobi, Inc. Dr Edward Behrens is a consultant for Sobi, Inc. and receives grant support from Sobi, Inc. Dr Deepika Bhatla, Dr John Carter, Dr May Chien, Dr Robert Cooper, Dr Lauren Draper, Dr Olive Eckstein, Dr J Allyson Hays, Dr Ashley Hinson, Dr Patricia Hobday, Dr Michael Isakoff, Dr Renee Modica, Dr Mona Riskalla, Dr Susmita Sarangi, and Dr Anand Tandra report no conflicts of interest.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing assistance was provided by Aparna Nori, PhD, CMPP, of rareLife solutions, and funded by Sobi, Inc.

Patient reviewers on this PLSP have received honorarium from Immunotherapy for their review work but have no other relevant financial relationships to disclose.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Emapalumab treatment in rheumatologic disease-associated hemophagocytic lymphohistiocytosis: a plain language summary

Affiliations

Emapalumab treatment in rheumatologic disease-associated hemophagocytic lymphohistiocytosis: a plain language summary

Authors

Affiliations

Plain language summary

Conflict of interest statement

LinkOut - more resources

Full Text Sources